The relationship between defects in lymphocyte production of transforming growth factor-β1 in systemic lupus erythematosus and disease activity or severity

Abstract

Transforming growth factor β (TGF-β) comprises of a family of proteins with pleiotropic signaling properties and potent immunoregulatory effects. In SLE we recently reported that lymphocyte production of the total and active forms of TGFβ1 was decreased. Here we asked whether these defects correlate with disease activity and/or severity. TGF-β1 production by blood lymphocytes from 17 prospectively studied SLE patients was compared with 10 rheumatoid arthritis (RA) patients and 23 matched healthy controls. The RA levels of active TGF-β1 were lower than controls, but were not deceased to the extent found in SLE. Levels of constitutive and anti-CD2 stimulated active TGF-β1 detected in picomolar amounts were markedly reduced in six untreated patients hospitalized with recent onset, very active and severe SLE and similarly reduced in 11 patients with treated, less active disease. By contrast, decreased production of total TGF-β1inversely correlated with disease activity. These studies suggest, therefore, that although impaired lymphocyte secretion of the latent precursor of TGF-β1 may result as a consequence of disease activity, a decreased capacity to convert the precursor molecule to its active form may pre-date disease onset. Insufficient exposure of T cells to picomolar concentrations of TGF-β1 at the time they are activated can result in impaired down-regulation of 1g synthesis. Therefore, decreased lymphocyte production of active TGF-β1 in SLE could be an immunologic defect which contributes to the B cell hyperactivity characteristic of this disease.